Macular degeneration is the leading cause of legal blindness in patients over the age of 55 in developed countries. In one study, nearly 28% of patients over 75 had some degree of macular degeneration. Other studies have suggested that a significant proportion of macular degeneration is heritable. This makes it possible to use a molecular genetic approach to identify genes that cause macular degeneration. Understanding this common disease at the molecular level has the potential to markedly improve the ability to diagnose and treat it in the future. The broad goal of the work proposed in this grant is to identify specific genes that cause inherited forms of macular disease including the common late-onset form of macular degeneration. The specific aims are to: 1) isolate and characterize the gene that causes Best's disease and refine the chromosomal location of a condition known as Dominant Macular Dystrophy with Flecks; 2) map the disease-causing genes in additional families with early and late-onset (age related) macular diseases; 3) investigate the potential allelic relationship between late-onset macular degeneration and earlier-onset dystrophies; 4) test a panel of "high priority" candidate genes for evidence of involvement in macular disease; and 5) explore the possibility that triplet repeats play a role in macular degeneration.